Nonlinear Dose Research Articles

Associations between dietary coenzyme Q10 intake and lipid profiles in adults: a national cross-sectional study

ObjectiveThis study aimed to determine the average intake of CoQ10 from dietary sources and explore the dose–response relationships between the dietary-derived CoQ10 intake and lipid profiles.MethodsWe performed a cross-sectional study based on the China Health and Nutrition Survey, which included 7,938 adults. The dietary intake assessment used three consecutive 24-h recalls combined with a household inventory. Serum was used for lipid profiling.ResultsThe average dietary-derived CoQ10 intake was 5.4 mg/day in Chinese adults. The dietary CoQ10 intake of the highest quartile (Q4 ≥ 6.96 mg/day) was negatively associated with total cholesterol (TC) [−0.12 (−0.19, −0.06) mmol/L], low-density lipoprotein cholesterol (LDL-C) [−0.17 (−0.23, −0.10) mmol/L], and non-high-density lipoprotein cholesterol (non-HDL-C) [−0.12 (−0.18, −0.05) mmol/L], while positively associated with apolipoprotein A-1 (ApoA1) [0.10 (0.08, 0.13) g/L] and triglycerides (TG) [0.14 (0.05, 0.23) mmol/L], compared to the lowest quartile (Q1 < 1.88 mg/day). Besides, dietary CoQ10 intake showed nonlinear dose–response associations with the above lipid variables (all Pnonlinear < 0.05).ConclusionDietary-derived CoQ10 intake may be associated with some lipid profiles, such as TG, ApoA1, TC, LDL-C, and non-HDL-C. However, CoQ10 from dietary sources may not be a good choice for individuals who need to CoQ10 supplement.

Association between the serum albumin–creatinine ratio and 28-day intensive care unit mortality among patients with sepsis: a multicenter retrospective cohort study

IntroductionSepsis is a substantial global health challenge with a considerable disease burden. Despite advancements in sepsis research, the mortality rates associated with this condition remain high. The relationship between the serum albumin-to-creatinine ratio (sACR) and mortality in patients with sepsis remains unclear. Therefore, this study aimed to investigate the association between the sACR and 28-day mortality in intensive care unit (ICU) patients with sepsis.MethodsIn this retrospective cohort study, we used data sourced from the eICU Collaborative Research Database. The primary exposure variable was sACR, and the primary outcome measure was mortality within 28 days after ICU admission. Statistical analyses included univariate and multivariate logistic regression models, generalized additive models, and two-piecewise linear regression models, which were employed to explore non-linear relationships and threshold effects between sACR and mortality.ResultsThe study cohort comprised 9,690 ICU patients with sepsis, with a 28-day mortality rate of 9.99%. The results of the multivariate logistic regression model indicated that elevated sACR levels were significantly associated with a reduced risk of mortality (odds ratio = 0.78, 95% confidence interval: 0.71–0.87, p < 0.001), even after adjusting for potential confounding variables. Curve fitting revealed a non-linear relationship between sACR and 28-day mortality, with an inflection point of 4.79.DiscussionThis study demonstrated that sACR is an independent risk factor for 28-day mortality in ICU patients with sepsis, exhibiting a non-linear negative dose–response relationship and a threshold effect. These findings may serve as early warning indicators in high-risk populations.

The association of serum albumin with 28 day mortality in critically ill patients undergoing dialysis: a secondary analysis based on the eICU collaborative research database

BackgroundThe relationship between serum albumin and prognosis in critically ill patients has been studied, however, there is a paucity of exploration into non-linear relationships, particularly in critically ill patients undergoing dialysis. This study intends to investigate the association between serum albumin (ALB) and 28 day mortality in critically ill patients undergoing dialysis.MethodsWe conducted a multi-center retrospective cohort study of patients undergoing dialysis by utilising data from the eICU Collaborative Research Database from 208 distinct ICUs across the United States between 2014 and 2015. The study focused on mortality within 28 days of ICU admission. We employed univariate analysis, multi-factor logistic regression, subgroup analysis, curve-fitting, and threshold effect analysis to examine the correlation between ALB levels and 28 day mortality.ResultsAmong the 2,315 patients with a median age of 63 years, 205 (8.86%) died within 28 days of ICU admission. When ALB level was < 2.7 g/dL, the mortality decreased with an adjusted odds ratio (OR) of 0.34 (95% CI 0.22–0.51, P < 0.0001) for every 1 increment in the ALB. However, no significant mortality changes were observed when ALB levels were at or above this threshold.ConclusionOur study identifies a nonlinear dose–response relationship between serum ALB levels and 28 day mortality in critically ill patients undergoing dialysis, with a specific turning point observed. This finding underscores a significant negative correlation between ALB levels and mortality risk, with lower ALB levels being associated with higher mortality risk in this particular population.

The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and non-alcoholic fatty liver disease in US adults: a cross-sectional study

The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (NHHR) is a novel lipid parameter used to assess the risk of cardiovascular disease. Previous studies have demonstrated an association between the NHHR and risk of non-alcoholic fatty liver disease (NAFLD). Owing to the lack of research exploring this relationship in specific populations, this study aimed to determine the potential link between the NHHR and risk of NAFLD among American adults in the United States. Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020. After excluding individuals with other liver diseases, alcohol abuse, and missing lipid data, a total of 6809 eligible adults were included for analysis. The NHHR was calculated as the ratio of (non-HDL-C) to HDL-C, while NAFLD was identified by liver steatosis detected by transient elastography. Multivariable weighted logistic regression models and restricted cubic spline (RCS) models were employed to investigate the relationship between the NHHR and risk of NAFLD. Subgroup and sensitivity analyses were also conducted to test the robustness of the results. As the NHHR increased, the prevalence of NAFLD rose progressively (5.88% vs. 8.75% vs. 12.24% vs. 15.77%, p < 0.001). In the overall population, after adjusting for confounding factors, each unit increase in the NHHR was associated with a 25% increase in NAFLD risk (OR = 1.25, 95% CI: 1.03–1.53, p = 0.0372). When the NHHR was analyzed as a categorical variable (quartiles), participants in the highest quartile had a significantly higher risk of NAFLD than those in the lowest quartile (OR = 2.6, 95% CI: 1.75–3.85, p = 0.009). RCS analysis further indicated a nonlinear dose–response relationship between the NHHR and risk of NAFLD (p non-linearity < 0.0001). This association remained significant in both subgroup and sensitivity analyses. This study confirmed that the NHHR, particularly at higher levels, was an independent risk factor for NAFLD. As a comprehensive lipid indicator, the NHHR had the potential to predict NAFLD risk. These findings provided new insights for the prevention and clinical management of NAFLD.

7542 Androgen Receptor Oligomerization State Allows Cells to Exhibit Non-Linear Dose Responses to Androgens Resulting in Distinct Biological Outputs

Abstract Disclosure: R. Safi: None. S.E. Wardell: None. P. Watkinson: None. X. Qin: None. M. Lee: None. S. Park: None. T. Krebs: None. E. Dolan: None. T. Tsuji: None. S. Nayak: None. M. Khater: None. M. Newlin: None. M. Kirkland: None. Y. Xie: None. H. Long: None. E. Fink: None. S.W. Fanning: None. S. Runyon: None. M. Brown: None. S. Xu: None. K. Owzar: None. J.D. Norris: None. D.P. McDonnell: None. An unanswered fundamental question in androgen action is how cells recognize and respond in a non-linear fashion to different levels of androgens to elicit distinct biological outputs such as occurs in prostate cancer (PCa) cells. Indeed, most PCa express the androgen receptor (AR), and tumor growth and progression are facilitated by exceedingly low levels of systemic or intratumorally produced androgens. Paradoxically, high dose androgens have been used to treat patients with late-stage metastatic PCa. We have determined that androgen dose regulates the relative cellular abundance of AR monomers and dimers in cells and that the biological output of each oligomeric form of the receptor is different. Using in vitro systems that model exposure from castrate (low dose; LD) to eugonadal levels and above (high dose; HD) of androgens, we have determined that the global changes in gene expression are substantially different, with the changes induced by LD androgens (monomeric AR) being associated with cell proliferation, and HD androgens (dimeric AR) inducing a differentiated phenotype. A similar distinction in response to androgen levels was observed in vivo. Using a chemical biology strategy, we identified ligands which freeze AR in a monomeric form and demonstrate that these compounds faithfully recapitulate the LD biology exhibited by physiological AR agonists. Mechanistically, we determined that monomeric AR facilitates a non-genomic activation of the mTOR signaling pathway to drive proliferation, while the dimer suppresses c-MYC expression, inhibit proliferation, and drive a transcriptional program associated with a differentiated phenotype. These findings highlight the inherent liabilities in current approaches used to inhibit AR-action in prostate cancer and are instructive as to strategies that can be used to develop new therapeutics for this disease and other androgenopathies. Presentation: 6/3/2024

Modulating the unfolded protein response with ISRIB mitigates cisplatin ototoxicity

Cisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin, and UPR marker gene expression and cell death measured. Treatment with ISRIB (Integrated Stress Response InhIBitor), a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested for its ability to reduce apoptosis in HEK cells, hair-cell death in cochlear cultures, and hearing loss using an in vivo mouse model of cisplatin ototoxicity. Finally, to evaluate whether ISRIB might interfere with cisplatin chemoeffectiveness, we tested it in head and neck squamous cell carcinoma (HNSCC) cell-based assays of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose–response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatin’s cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.

Dose increment in ultrashort particle irradiations via coherent stopping power

We present a relativistic self-consistent theory of the coherent stopping power (CSP) of ultradense charged particle beams propagating in a dense matter. CSP corresponds to a collective inelastic collision which adds to the ordinary stopping power of individual particles. Unlike the latter, which depends only on the particles' energy, CSP depends upon many more parameters such as the total charge of the ensemble and its charge density and shape. This paves the way for a broad variety of novel methods to tailor particle absorption and penetration in a dense matter. CSP losses can be explained both by collective excitations of single or multiple molecules and by the emission of coherent Cherenkov radiation. Here we demonstrate that the former mechanism is more relevant than the latter. We find that the coherent energy absorption of subpicosecond particle bunches in water occurs exciting a broad Debye process in the GHz range and an intermolecular stretching vibration mode in the THz region. We generalize the Bethe-Bloch stopping power formula to coherent effects including self-forces, dielectric screening, and absorption by the dense matter. For the sake of a self-consistent dynamical theory including phase space evolution, we have also generalized the Fermi-Eyges theory of particle diffusion to the presence of forces. Nonlinear dynamics is demonstrated, inducing nonlinear dose release, beam self-focusing, and self-enhancement of coherent losses. Given the advent of ultraintense particle sources and their use for biomedical and other relevant applications, our results may be of paramount importance for contemporary and future developments of science and technology. Published by the American Physical Society 2024

The Dynamics of Methylation Concentrations in Glutathione Peroxidase 3 Promoter from Patients with Chronic Heart Failure and Their Association with Key Clinical Parameters

ObjectiveThis study investigated changes in methylation concentrations within the glutathione peroxidase 3 (GPX3) promoter region among patients diagnosed with chronic heart failure (CHF). Peripheral blood samples were collected from 20 CHF patients and 20 healthy individuals for analysis. MethodsUsing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, methylation concentrations of 11 CpG sites within the GPX3 promoter region were quantified. ResultsResults showed a significant increase in methylation at the GPX3_FA10_CpG_24 site in patients with CHF compared with the control group (P < 0.05). Furthermore, a nonlinear dose–response relationship was observed between methylation concentrations at this site and key clinical parameters including serum apolipoprotein A-1, D-dimer, chlorine, potassium, and sodium (Na) (P < 0.05). ConclusionsThese findings suggest that aberrant methylation of the GPX3 promoter may impact disease progression by influencing physiological functions such as blood lipids, coagulation, and electrolytes. Further investigations are warranted to elucidate the role of GPX3 promoter methylation in CHF pathogenesis, potentially contributing valuable insights for its prevention, diagnosis, and treatment.

Phytochemicals Analysis, In vitro Anti-plasmodium Activity of Delonix regia Bark and Carica papaya Leaf Extracts in Combination with Chloroquine

Background: The effectiveness of treating malaria may be jeopardized by artemisinin-resistant parasites. Pharmaceutical companies have been using plants for a very long time to generate the prototype molecules needed to treat Plasmodium infections. Objective: To evaluate anti-plasmodial potency of extracts of Delonix regia and Carica papaya when used in combinations with chloroquine. Methods: The plants were collected from Homa-Bay County in Kenya, dried under shade to a consistent weight, and then milled into a fine powder. Organic solvents were then used for extraction. After phytochemical screening of the extracts was conducted, In vitro tests were done on the extracts against Plasmodium falciparum, with a starting concentration of 100µg/mL. To prepare the test concentration ranges, the extracts were serially diluted 2-fold in growth medium. In a sealed gas chamber, the assay plates were incubated at 370C for 72 hours with 3% O2 and 4% CO2 with N2 as the balance. By comparing each well's absorbance to that of a well that contained the drug-free control, the number of parasites still present at each concentration of the test substance were ascertained. Plotting survival against concentration enabled the determination of the IC50 values by a non-linear dose response curve fitting. Results: In this investigation, the extracts from Delonix regia showed significant synergism (based on IC50 shifts) with CQ for both the ethyl acetate and methanol extracts with the exception of the highest combination dosage. Carica papaya extracts were much improved by the presence of CQ; however, this was not consistently reflected in the corresponding CQ IC50. Conclusion: The results of this study which revealed synergism between the study plants extracts and chloroquine, support the reasons why some traditional healers have started combining medicinal herbs with chloroquine to boost its potency.

Association between composite dietary antioxidant index and cardiovascular health: Results from two observational studies

BackgroundThe effect of dietary antioxidant capacity on health has attracted increasing attention, but unequivocal evidence for its benefits on cardiovascular diseases is still lacking. ObjectivesOur aim was to assess the association between composite dietary antioxidant index (CDAI) and Life’s Essential 8 (LE8), an evaluation indicator of cardiovascular health (CVH), in two large cohorts. MethodsThe cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 and Community Cohort Study on Specialized Nervous System Diseases (CCSNSD) 2018. The relationship between CDAI and CVH was studied by multinomial logistic regression, restricted cubic spline, subgroup and sensitivity analysis. ResultsAfter adjusting for all potential confounding factors, it suggested that higher CDAI was positively associated with higher CVH (NHANES: OR Q4 vs. Q1 = 0.19, 95 % CI: 0.14–0.25; CCSNSD: OR Q4 vs. Q1 = 0.03, 95 % CI: 0.03–0.04). And a nonlinear dose–response relationship between CDAI and CVH was observed in two large cohorts. The robustness of the results was further demonstrated by sensitivity analysis. Among them, Mendelian randomization analysis showed that higher Vitamin C and Vitamin E intakes were causally associated with a lower risk of CVD. Moreover, there was a stronger positive correlation between the CDAI and CVH among individuals with lower socioeconomic status in both cohorts. ConclusionOur findings demonstrated the potential benefit of dietary antioxidant intake in improving CVH. Besides, the relationship between CDAI and CVH may be influenced by income levels, highlighting the need for targeted interventions in populations with low income to increase CVH levels.

Association of Life’s Essential 8 with metabolic dysfunction-associated steatotic liver disease (MASLD), a cross-sectional study from the NHANES 2003–2018

There is limited research on the relationship between Life's Essential 8 (LE8) score and metabolic dysfunction-associated steatotic liver disease (MASLD). Our aim is to investigate the relationship between overall lifestyle assessed by LE-8 score and MASLD in a nationally representative sample. We employed the LE8 score to comprehensively evaluate cardiovascular health, the assessment of MASLD primarily utilized the Fatty Liver Index. The weighted logistic regression models, restrictive cubic splines (RCS), subgroup analyses and the weighted quantile sum (WQS) regression were used to evaluate the relationship between the cardiovascular health and MASLD. Logistic regression models revealed that higher LE8 scores were associated with lower odds of having MASLD. The RCS revealed a significant nonlinear dose–response relationship between LE8 scores and MASLD. The WQS regression model indicated that blood glucose contributed the most to the risk of MASLD. The subgroup analysis indicates that there are significant differences in this association across age, educational level, and poverty income ratio. Our study suggests that an inverse correlation between LE8 and the risk of MASLD. Our findings underscore the utility of the LE8 algorithm in MASLD risk assessment and provide support for MASLD prevention through the promotion of healthy lifestyles.

Association between obstructive sleep apnea severity and depression risk: a systematic review and dose-response meta-analysis.

Obstructive sleep apnea (OSA) has received considerable attention as a potential risk factor for depressive symptoms. The systematic review was conducted to confirm the dose‒response connection between OSA severity and depression risk. A systematic literature search of English and Chinese articles published in PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and SinoMed databases from their inception to 28 August 2023 was conducted. An evaluation using the Newcastle‒Ottawa Scale was performed. A meta-analysis was used to evaluate the impact of OSA severity. A random-effects dose‒response model was conducted to evaluate the linear and nonlinear dose‒response connections. We evaluated publication bias by funnel plots, and symmetry by Egger's test. We identified 18 cross-sectional researches. 3143 participants which were involved in the dose‒response meta-analysis. Contrasted with mild OSA, individuals with severe OSA had a higher adjusted risk of depression (rate ratio: 1.34, 95% confidence interval = 1.05-1.70), with substantial heterogeneity (I2 = 70.9%, Pheterogeneity<0.001). There is a significant linear connection between OSA severity and depression risk. The depression risk increased by 0.4% for every 1 event per hour increase in the apnea-hypopnea index (AHI). The protocol for this unfunded research was drafted and registered at PROSPERO (ID CRD42023474097).

Effects of cigarette smoking associated with sarcopenia in persons 60 years and older: a cross-sectional study in Zhejiang province

PurposeSmoking is a risk factor for sarcopenia. Nevertheless, few studies analyzed the independent effects of various smoking dimensions (duration, intensity, cumulative dose) on sarcopenia risk. This is a cross-sectional study based on an older population in Zhejiang Province to determine which smoking dimensions are mainly important for sarcopenia risk and to explore the dose–response relationship between them.MethodsOur study included 783 patients with sarcopenia and 4918 non-sarcopenic individuals. Logistic regression and restricted cubic with logistic regression (for nonlinear dose effects) were used to obtain odds ratios (ORs) and 95% confidence intervals as well as restricted cubic splines (RCS) curves.ResultsCompared with never-smokers, current smokers had an increased risk of sarcopenia (OR = 1.786; 95% CI 1.387–2.301) after adjusting for confounders such as age, sex, education, alcohol consumption, disease history, etc. There was no significant association between smoking intensity and sarcopenia after more than 20 cigarettes per day (OR = 1.484; 95% CI 0.886–2.487), whereas the risk of sarcopenia increased significantly with increasing duration of smoking after more than 40 years (OR = 1.733; 95% CI 1.214–2.473). Meanwhile, there was a significant non-linear dose–response relationship between smoking duration or intensity and the risk of sarcopenia. However, the risk of sarcopenia increased linearly with the number of pack-years of smoking, which is not a significant nonlinear dose–response relationship.ConclusionsThis study indicated the association between smoking and sarcopenia. Both smoking duration and cumulative dose were significantly and positively associated with sarcopenia. These findings reflect the important role of the number of years of smoking in increasing the risk of sarcopenia and provide scientific evidence that different smoking dimensions may influence the risk of the sarcopenia.

Investigating the determinants of fear of cancer recurrence in patients with early‐stage non‐small cell lung cancer: Insights from a restricted cubic spline model

AbstractObjectiveThis study aims to investigate the determinants and the dose–response relationship of fear of cancer recurrence among patients with early‐stage non‐small cell lung cancer (NSCLC), aiming to inform prevention and intervention strategies.MethodsEmploying a cross‐sectional design, we analyzed data from 677 postoperative NSCLC patients who received treatment at National Cancer Center between January 2022 and August 2023. Data collection involved a general demographic survey, the Fear of Progression Questionnaire‐Short Form, Hope Herth Index, and Social Support Rating Scale. We employed logistic regression and restricted cubic spline models to identify factors influencing fear of recurrence (FCR).ResultsUnivariate regression analysis identified female gender and having minor children as significant risk factors, while being older than 60, a higher income, and elevated levels of hope and social support emerged as protective factors. Multivariate logistic regression revealed age (OR = 0.392, 95% CI 0.205–0.750), monthly income (OR = 0.016, 95% CI 0.315–0.886), hope level (OR = 0.305, 95% CI 0.187–0.496), and social support (OR = 0.584, 95% CI 0.375–0.908) as independent influencers of recurrence fear. The restricted cubic spline model indicated a nonlinear impact of hope and social support on this fear.ConclusionAnalysis using the restricted cubic spline model underscores the influence of age, income, hope, and social support on FCR, with a nonlinear dose–response relationship evident between hope, social support, and fear. Prioritizing the enhancement of social support before increasing hope levels can rapidly and effectively alleviate FCR.

Investigation of biological-rhythm patterns: physiological and biochemical effects in herbaceous plants exposed to low-level chronic radiation – part 1: nonirradiated seeds

Hypothesis Because reactive oxygen species are involved in the regulation of biological rhythms, we hypothesized that intra-annual variability of seed progeny quality at low doses of ionizing radiation (LDIRs) would differ from that of background plants. Materials and methods We conducted 12 consecutive experiments using the roll culture method by germinating seeds (monthly for 3 weeks) of six herbaceous plant species (Bromus inermis, Geum aleppicum, Plantago major, Rumex confertus, Silene latifolia, and Taraxacum officinale) growing under conditions of chronic radiation in the East Ural Radioactive Trace (EURT). We assessed physiological (seed viability and abnormality frequency) and biochemical (low-molecular-weight antioxidants, LMWAs) parameters of seedlings. Results Total absorbed dose rates of maternal plants (TADRplants) and seed embryos (TADRseeds) in the EURT exceeded background levels by 1–3 and 1–2 orders of magnitude, respectively. Nonlinear dependencies on TADR were mainly characteristic of physiological and biochemical parameters. For most populations of the studied species (B. inermis, G. aleppicum, R. confertus, and S. latifolia), seedling survival and root length decreased in the autumn–winter period, while the frequency of abnormal seedlings increased. The content of LMWAs could be ranked as R. confertus > B. inermis > G. aleppicum > S. latifolia, in good agreement with the presence of anthocyanin pigmentation in the plants. The lowest synthesis of antioxidants in seedlings was observed in winter. A high LMWA content promoted growth and reduced the frequency of abnormal seedlings. Conclusions These results underscore a multistage nature of the impact of LDIRs on intra-annual biological rhythms in plants. High heterogeneity in reference group ‘wild grasses’ and diversity of their radiobiological effects should help to develop methods of radiation protection for natural ecosystems and facilitate approaches used by the International Commission on Radiological Protection. Highlights Absorbed dose rates for six plant species in the East Ural Radioactive Trace (EURT) area range from 0.11 to 73.89 µGy h−s (plants) and 0.11 to 6.88 µGy h−s (seed embryos). Intra-annual rhythms of physiological and biochemical parameters in the EURT zone differ from those in background seedlings. Plants in the EURT area exhibit a wide range of trait variability, asynchrony of the manifestation of the effects, nonlinear dose–response relations, and hormesis. A high content of low-molecular-weight antioxidants (LMWAs) is associated with low frequency of developmental abnormalities and high viability of seed progeny.

Non-linear association and benchmark dose of blood pressure on carotid artery intima-media thickening in a general population of southern China.

This study aimed to evaluate whether there is a J-curve association between blood pressure (BP) and carotid artery intima-media thickening (CAIT) and estimate the effect of the turning point of BP on CAIT. Data from 111,494 regular physical examinations conducted on workers and retirees (aged 18 years or older) between January 2011 and December 2016, exported from the hospital information system, were analyzed. Restricted cubic splines (RCS) logistic regression was employed to access the association of BP with CAIT, and Bayesian benchmark dose methods were used to estimate the benchmark dose as the departure point of BP measurements. All the pnon-linear values of BP measurements were less than 0.05 in the RCS logistic regression models. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) had J-curve associations with the risk of CAIT at a turning point around 120/70 mmHg in the RCS. The benchmark dose for a 1% change in CAIT risk was estimated to be 120.64 mmHg for SBP and 72.46 mmHg for DBP. The J-curve associations between SBP and DBP and the risk of CAIT were observed in the general population in southern China, and the turning point of blood pressure for significantly reducing the risk of CAIT was estimated to be 120.64/72.46 mmHg for SBP/DBP.

Association between kidney stones and life's essential 8: a population-based study

BackgroundKidney stones exhibit a robust correlation with cardiovascular disease (CVD). The objective of this research is to investigate the correlation between kidney stones and Life's Essential 8 (LE8), a newly updated assessment of cardiovascular health (CVH), among adults in the United States.MethodsIn this study, which analyzed data from the 2007–2018 National Health and Nutrition Examination Survey, we employed LE8 scores (ranging from 0 to 100) as the independent variable, classifying them into low, moderate, and high CVH categories. The research examined the relationship between LE8 scores and kidney stones by using multivariate logistic regression and restricted cubic spline models, with kidney stones as the dependent variable.ResultsOut of the 14,117 participants in this research, the weighted mean LE8 score was 69.70 ± 0.27. After accounting for confounding factors, there was an inverse association between higher LE8 scores and the likelihood of developing kidney stones (OR of 0.81 per 10-point increase, with a 95% confidence interval of 0.77–0.85), demonstrating a non-linear dose–response pattern. Similar patterns were observed for health behaviors, health factor scores, and kidney stones. Stratified analyses demonstrated a stable negative correlation between LE8 scores and kidney stones across different subgroups.ConclusionLE8 and its subscale scores exhibited a robust and inverse correlation with the occurrence of kidney stones. Encouraging adherence to optimal CVH levels has the potential to serve as an effective strategy in preventing and minimizing the occurrence of kidney stones.

Predictive value of lactate dehydrogenase for Mycoplasma pneumoniae necrotizing pneumonia in children based on decision curve analysis and dose–response analysis

Mycoplasma pneumoniae necrotizing pneumonia (MPNP) has a long and severe disease course, which seriously threatens to jeopardize patients' lives and health. Early prediction is essential for good recovery and prognosis. In the present study, we retrospect 128 children with MPNP and 118 children with Mycoplasma pneumoniae pneumonia combined with pulmonary consolidation to explore the predictive value of lactate dehydrogenase (LDH) in children with MPNP by propensity score matching method, multiple logistic regression analysis, dose–response analysis and decision curve analysis. The WBC count, PLT count and percentage of neutrophils were significantly higher in necrosis group than consolidation group. The serum CRP, PCT, ESR, D-D, FIB, ALT, LDH, IgG and IgM were significantly higher in necrosis group. Compared to consolidation group, necrosis group is more severe in chest pain and dyspnea. Multivariate logistic regression analysis showed that duration of LDH levels, high fever, d-dimer, and fibrinogen were independent predictive factors for the incidence of MPNP. Restricted cubic spline analysis showed that a non-linear dose–response relationship between the continuous changes of LDH level and the incidence of MPNP. Decision curve analysis revealed that LDH had an important clinical value in predicting MPNP. This study provides a potential serologic indicator for early diagnosis of MPNP.

Chronic kidney disease and cognitive performance: NHANES 2011–2014

PurposePrevious studies suggest an association between chronic kidney disease (CKD) and cognitive impairment. The purpose of this study was to explore the association between the diverse stages of CKD and the cognitive performance of elderly American adults.MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were used. Multivariate adjusted logistic regression, subgroup analysis, and the restricted cubic spline model were used to assess the associations of CKD stage and estimated glomerular filtration rate (eGFR) with cognitive performance. The measures used to evaluate cognitive function included the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the Animal Fluency test, and the Digit Symbol Substitution test (DSST).ResultsThis study included 2234 participants aged ≥ 60 years. According to the fully adjusted model, stages 3–5 CKD were significantly associated with the CERAD test score (OR = 0.70, 95% CI [0.51, 0.97], p = 0.033), the Animal Fluency test score (OR = 0.64, 95% CI [0.48, 0.85], p = 0.005), and the DSST score (OR = 0.60, 95% CI [0.41, 0.88], p = 0.013). In addition, the incidence of poor cognitive function increased with decreasing eGFR, especially for individuals with low and moderate eGFRs. Both the DSST score (p nonlinearity < 0.0001) and the Animal Fluency test score (p nonlinearity = 0.0001) had nonlinear dose–response relationships with the eGFR. However, a linear relationship was shown between the eGFR and CERAD test score (p nonlinearity = 0.073).ConclusionsCKD, especially stages3–5 CKD, was significantly associated with poor cognitive performance in terms of executive function, learning, processing speed, concentration, and working memory ability. All adults with CKD should be screened for cognitive impairment.

Correlation of dietary inflammation index and dietary pattern with mild cognitive impairment in patients with type 2 diabetes

ObjectiveWe aimed to determine the dietary patterns associated with mild cognitive impairment (MCI) in type 2 diabetes (T2DM) and the correlation of dietary inflammatory index (DII) with MCI. MethodsThe Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. A semi-quantitative food frequency questionnaire was used to collect dietary data and calculate DII. Dietary patterns were determined by reduced-rank regression (RRR), grouping dietary pattern scores and DII into quartiles, with logistic regression for correlation analysis. Dose–response relationships between dietary pattern scores, DII and diabetic MCI were explored using restricted cubic splines (RCS). A mediation analysis was performed to investigate whether DII mediates the association between dietary patterns and MCI. ResultsIn the “Mediterranean-style dietary pattern”, the multivariable-adjusted odds ratio of having MCI was 0.37 (95% CI: 0.20–0.68; p for trend=0.002) in the highest versus lowest quartiles of the dietary score. In the “high-meat and low-vegetable pattern”, the multivariable-adjusted odds ratio of having MCI was 6.84 (95% CI: 3.58–13.10; p for trend<0.001) in the highest versus lowest quartiles of the dietary score. In the “Western-style dietary pattern”, the multivariable-adjusted odds ratio of having MCI was 2.48 (95% CI: 1.38–4.46; p for trend=0.001). The multivariable-adjusted odds ratio of having MCI was 3.99 (95% CI: 2.14–7.42; p for trend<0.001) in the highest versus lowest quartiles of DII.There is a non-linear dose–response relationship between the “high-meat and low-vegetable pattern” score and the prevalence of MCI, as well as the DII and the prevalence of MCI. The DII partially mediated the impact of the “Mediterranean-style dietary pattern” and the “high-meat and low-vegetable pattern” on MCI. ConclusionIn T2DM patients, greater adherence to the “Mediterranean-style dietary pattern” is associated with a lower probability of having MCI. However, excessive consumption of meat, especially red meat and processed meat, combined with a lack of vegetable intake, is associated with a higher probability of having MCI. Greater adherence to the “Western-style dietary pattern” is associated with a higher probability of having MCI. In addition, a pro-inflammatory diet is associated with a higher probability of having MCI, and DII partially mediates the impact of dietary patterns on MCI.